Cutting edge:: NKT cells constitutively express IL-23 receptor and RORγt and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion
Cutting edge:: NKT cells constitutively express IL-23 receptor and RORγt and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion
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DOI：
10.4049/jimmunol.180.8.5167
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发表时间：
2008-04-15
影响因子：
4.4
通讯作者：
Caspi, Rachel R.
中科院分区：
文献类型：
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作者：
Rachitskaya, Aleksandra V.;Hansen, Anna M.;Caspi, Rachel R.
Th17细胞需要IL-6和转化生长因子β来维持血统，需要IL-23来维持。出乎意料的是，在抗CD3和IL-23刺激下，幼稚的IL-6(-/-)脾细胞在培养的头24小时内产生了正常数量的IL-17。这些快速产生IL-6的IL-17被鉴定为主要是DX5+TCRβ(+)NKT细胞，使用不变的NKT特异性配体半乳糖神经酰胺可以发现类似的反应。人类NKT细胞也产生IL-17。NKT细胞固有地表达IL-23R和ROR-γt。TCR或IL-23R的结扎均可触发IL-17的产生，两者具有协同作用，提示存在独立但趋同的途径。IL-17的产生不限于特定的NKT细胞亚群，但它们是NK1.1阴性的。重要的是，体内注射半乳糖神经酰胺会在脾内引发快速的IL-17反应。这些数据表明，NKT细胞先于适应性IL-17快速产生IL-17具有重要的生物学作用。
Th17 cells require IL-6 and TGF beta for lineage commitment and IL-23 for maintenance. Unexpectedly, naive IL-6(-/-) splenocytes stimulated with anti-CD3 and IL-23 produced normal amounts of IL-17 during the first 24 h of culture. These rapid IL-6-independent IL-17 producers were identified as predominantly DX5+ TCR beta(+) NKT cells, and a comparable response could be found using the invariant NKT-specific ligand a galactosylceramide. Human NKT cells also produced IL-17. NKT cells constitutively expressed IL-23R and ROR gamma t. Ligation of either TCR or IL-23R triggered IL-17 production and both together had a synergistic effect, suggesting independent but convergent pathways. IL-17 production was not restricted to a particular subset of NKT cells but they were NK1.1 negative. Importantly, in vivo administration of a galactosylceramide triggered a rapid IL-17 response in the spleen. These data suggest an important biological role for innate IL-17 production by NKT cells that is rapid and precedes the adaptive IL-17 response.